Regioselective Synthesis of a C-4 Carbamate,C-6 n-Pr Substituted Cyclitol Analogue of SL0101

An asymmetric synthesis of two analogues of SL0101 (1) has been achieved. The effort is aimed at the discovery of inhibitors of the p90 ribosomal S6 kinase (RSK) with improved bioavailability. The route relies upon the use of the Taylor catalyst to regioselectively install C-3 '' acetyl or carbamate functionality. This study led to the identification of a third-generation analogue of SL0101 with a C-4 '' n-Pr-carbamate and a C-3 '' acetate with improved RSK inhibitory activity.